Analytical validation of protein biomarkers for risk of spontaneous preterm birth
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ABSTRACT:
SUBMITTER: Bradford C
PROVIDER: S-EPMC11322780 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
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Project description:Transcriptome analysis of preterm and term placentas
2021-08-10 | GSE120480 | GEO
Project description:BackgroundSpontaneous preterm birth (sPTB) stands as a leading cause of neonatal mortality. Consequently, preventing sPTB has emerged as a paramount concern in healthcare. Therefore, our study aimed to develop a nomogram, encompassing patient characteristics and cervical elastography, to predict sPTB in singleton pregnancies. Specifically, we targeted those with a short cervix length (CL), no history of sPTB, and who were receiving vaginal progesterone therapy.MethodsA total of 568 patients were included in this study. Data from 392 patients, collected between January 2016 and October 2019, constituted the training cohort. Meanwhile, records from 176 patients, spanning November 2019 to January 2022, formed the validation cohort. Following the univariate logistic regression analysis, variables exhibiting a P-value less than 0.05 were integrated into a multivariable logistic regression analysis. The primary objective of this subsequent analysis was to identify the independent predictors linked to sPTB in the training cohort. Next, we formulated a nomogram utilizing the identified independent predictors. This tool was designed to estimate the likelihood of sPTB in singleton pregnancies, particularly those with a short CL, devoid of any sPTB history, and undergoing vaginal progesterone therapy. The C-index, Hosmer-Lemeshow (HL) test, calibration curves, decision curve analysis (DCA), and receiver operating characteristic (ROC) were used to validate the performance of the nomogram.ResultsUpon finalizing the univariate analysis, we progressed to a multivariable analysis, integrating 8 variables with P < 0.05 from the univariate analysis. The multivariable analysis identified 7 independent risk factors: maternal age (OR = 1.072; P < 0.001), cervical length (OR = 0.854; P < 0.001), uterine curettage (OR = 7.208; P < 0.001), GDM (OR = 3.570; P = 0.006), HDP (OR = 4.661; P = 0.003), C-reactive protein (OR = 1.138; P < 0.001), and strain of AI (OR = 7.985; P < 0.001). The nomogram, tailored for sPTB prediction, was grounded on these 7 independent predictors. In predicting sPTB, the C-indices manifested as 0.873 (95% CI, 0.827-0.918) for the training cohort and 0.916 (95%CI, 0.870-0.962) for the validation cohorts, underscoring a good discrimination of the model. Additionally, the ROC curves served to evaluate the discrimination of nomogram model across both cohorts. Calibration curves were delineated, revealing no statistically significant differences in both the training (χ2 = 5.355; P = 0.719) and validation (χ2 = 2.708; P = 0.951) cohorts as evidenced by the HL tests. Furthermore, the DCA underscored the model's excellence as a predictive tool for sPTB.ConclusionsBy amalgamating patient characteristics and cervical elastography data from the second trimester, the nomogram emerged as a visually intuitive and dependable tool for predicting sPTB. Its relevance was particularly pronounced for singleton pregnancies characterized by a short CL, an absence of prior sPTB incidents, and those receiving vaginal progesterone therapy.
| S-EPMC10543363 | biostudies-literature
Project description:Biochemistry of spontaneous preterm birth
| PRJNA493125 | ENA
Project description:IntroductionPreterm birth (PTB) remains the leading cause of neonatal morbidity and mortality in the United States. The mechanisms underlying spontaneous PTB (SPTB) involve multiple physiological processes and molecular transformations at the level of the placenta. This study aimed to identify consistent molecular correlates in the placenta linked with SPTB by cross-examining publicly available transcriptomic datasets within two publicly available repositories.MethodsThe National Center for Biotechnology Information and the European Bioinformatics Institute were queried, and relevant datasets were independently normalized, and then merged based on similarity in design. Differentially expressed genes between SPTB and term delivery (TD) were identified using a fixed effects linear model (p < 0.0001) and were evaluated for enrichment of biological processes and pathways. In general, global signatures associated with SPTB were unique to each study.ResultsA total of three datasets were used in the meta-analysis to assess the placental transcriptome in SPTB (11 samples) as compared to TD (15 samples). We identified 174 differentially expressed genes consistently correlated with SPTB across all studies, including previously proposed and new candidate biomarkers of SPTB. Differentially expressed genes were significantly enriched for master regulatory pathways relevant to placental development and disease, including chromatin organization and cellular response to stress.DiscussionIdentification of differentially expressed genes and associated pathways across multiple studies may identify transcriptomic biomarkers that can be applied in clinical investigations of SPTB and provide researchers enhanced insight into the underlying etiologies of SPTB.
| S-EPMC9715015 | biostudies-literature
Project description:A biomarker is a biological measure predictive of a normal or pathogenic process or response. Biomarkers are often useful for making clinical decisions and determining treatment course. One area where such biomarkers would be particularly useful is in identifying women at risk for preterm delivery and related pregnancy complications. Neonates born preterm have significant morbidity and mortality, both in the perinatal period and throughout the life course, and identifying women at risk of delivering preterm may allow for targeted interventions to prevent or delay preterm birth (PTB). In addition to identifying those at increased risk for preterm birth, biomarkers may be able to distinguish neonates at particular risk for future complications due to modifiable environmental factors, such as maternal smoking or alcohol use during pregnancy. Currently, there are no such biomarkers available, though candidate gene and epigenome-wide association studies have identified DNA methylation differences associated with PTB, its risk factors and its long-term outcomes. Further biomarker development is crucial to reducing the health burden associated with adverse intrauterine conditions and preterm birth, and the results of recent DNA methylation studies may advance that goal.
| S-EPMC4846845 | biostudies-literature
Project description:Twin pregnancies are associated with a three-fold greater perinatal mortality than singleton pregnancies. Prematurity is a main contributor, with 50% of twin pregnancies delivering before 37 weeks and 10% delivering before 32 weeks of gestation.The aetiology of preterm delivery in twin pregnancies is likely multifactorial and different from that of singletons.Cervical cerclage reduces preterm birth rates in singletons but has mixed results in twins with some studies showing harm.The use of progesterone to prevent preterm birth in singletons has conflicting results and has not been proven to prevent preterm birth in twins. Studies continue to determine whether the cervical pessary is effective in preventing preterm birth in multiple pregnancies.There is a paucity of data available on the prevention of preterm birth in triplets/higher order multiples but similar principles to twin pregnancy apply.To review the burden of preterm birth in multiple pregnancy.To understand the methods available for preventing preterm birth in multiple pregnancies and the evidence surrounding the use of each one.To be aware of the use of the Arabin pessary.
| S-EPMC6034359 | biostudies-other
Project description:Severe preeclampsia is accompanied by many complications, which is extremely harmful to pregnant women and fetuses. However, in the classification of preterm birth, it is generally divided into spontaneous preterm birth and therapeutic preterm birth, and insufficient attention has been paid to preterm birth in severe preeclampsia. This article aims to explore the clinical difference between preterm birth in severe preeclampsia and spontaneous preterm birth. In the experiment, this paper selected pregnant women who delivered and were treated in a hospital from April 2010 to April 2020 as cases. In terms of grouping, not only are they divided into severe eclampsia group (observation group 1), spontaneous preterm birth group (observation group 2), and general delivery group (control group) according to the cause of premature birth, but also according to the gestational age of severe eclampsia onset, preterm weeks, and other groups. Not only the clinical difference between severe preeclampsia preterm birth and spontaneous preterm birth was compared horizontally, but also the factors affecting the complications of preterm pregnant women, perinatal asphyxia rate, and mortality were longitudinally analyzed. The experimental results in this paper showed that there were significant differences in maternal complications and neonatal mortality between the severe preeclampsia preterm group and the spontaneous preterm group (P < 0.05). In addition, the severe preeclampsia preterm birth group was more harmful than the spontaneous preterm birth group. The complication rate of the severe preeclampsia preterm birth group was 10% higher than that of the spontaneous preterm birth group, and the neonatal mortality rate was 2% higher.
| S-EPMC9499783 | biostudies-literature
Project description:BACKGROUND:Specialised preterm birth clinics care for women at high risk of spontaneous preterm birth. This systematic review assesses current practice within preterm birth clinics globally. METHODS:A comprehensive search strategy was used to identify all studies on preterm birth clinics on the MEDLINE, Embase, PsycINFO, CENTRAL and CINAHL databases. There were no restrictions to study design. Studies were limited to the English language and publications from 1998 onwards. Two reviewers assessed studies for inclusion, performed data extraction and reviewed methodological quality. Primary outcomes were referral criteria, investigations and interventions offered in preterm birth clinics. Secondary outcomes were the timing of planned first and last appointments and frequency of review. RESULTS:Thirty-two records fulfilled eligibility criteria and 20 studies were included in the main analysis following grouping of records describing the same study or clinic. Studies were of mixed study design and methodological quality. A total of 39 clinics were described; outcome data was not available for all clinics. Referral criteria included previous spontaneous preterm birth (38/38, 100%), previous mid-trimester loss (34/38, 89%) and previous cervical surgery (33/38, 87%). All clinics offered transvaginal cervical length scans. Additional investigations varied, including urogenital swabs (16/28, 57%) and fetal fibronectin (8/28, 29%). The primary treatment of choice for a sonographic short cervix was cervical cerclage in 10/33 (30%) clinics and vaginal progesterone in 6/33 (18%), with 10/33 (30%) using multiple first-line options and 6/33 (18%) using a combination of treatments. The majority of clinics planned timing of first review for 12-16 weeks (30/35, 86%) and the frequency of review was usually determined by clinical findings (18/24, 75%). There was a wide variation in gestational age at clinic discharge between 24 and 37 weeks. CONCLUSIONS:There is variation in the referral criteria, investigations and interventions offered in preterm birth clinics and in the timing and frequency of review. Consistency in practice may improve with the introduction of consensus guidelines and national preterm birth prevention programmes. TRIAL REGISTRATION:Systematic review registration number: CRD42019131470.
| S-EPMC6990596 | biostudies-literature
Project description:The objective was to characterise cervical leukocyte populations and inflammatory mediators associated with term and recurrent spontaneous preterm birth (SPTB) in pregnant women with a history of SPTB. A prospective observational study was undertaken on 120 women with a history of SPTB. A cytobrush was used to sample cells from the cervix at 12-25 weeks' gestation. Cells were enumerated and characterised by flow cytometry. Cytokines and chemokines were also measured. Participants were then grouped according to delivery at term (>36+6 weeks), late SPTB (34-36+6 weeks) or early SPTB (<34 weeks). Differences in leukocyte sub-populations, cytokine and chemokine levels were compared with outcome. Cervical leukocytes comprised up to 60% of the host-derived cells. Most of these (90-100%) were polymorphonuclear cells (PMN). Most of the remaining cells were mucosal macrophages expressing CD68 and CD103 in addition to markers shared with blood-borne monocytes. Failure to detect cervical macrophages in at least 250,000 cervical epithelial cells was a feature of women who experienced early SPTB (6 out of 6 cases, 95% CI 61-100%) compared with 34% (30 out of 88 cases, 95% CI 25-43%, P<0.001) of women delivering after 34 weeks. CCL2 (MCP-1) was also low in SPTB before 34 weeks and levels above 75 ng/g and/or the presence of macrophages increased the specificity for birth after 34 weeks from 66% to 82% (55 out of 67 cases, 95% CI 73-91%). Absence of cervical macrophages and low CCL2 may be features of pregnancies at risk of early SPTB.
| S-EPMC4764650 | biostudies-literature
Project description:ObjectiveTo determine the risk of recurrent spontaneous preterm birth (sPTB) following sPTB in singleton pregnancies.DesignSystematic review and meta-analysis using random effects models.Data sourcesAn electronic literature search was conducted in OVID Medline (1948-2017), Embase (1980-2017) and ClinicalTrials.gov (completed studies effective 2017), supplemented by hand-searching bibliographies of included studies, to find all studies with original data concerning recurrent sPTB.Study eligibility criteriaStudies had to include women with at least one spontaneous preterm singleton live birth (<37 weeks) and at least one subsequent pregnancy resulting in a singleton live birth. The Newcastle-Ottawa Scale was used to assess study quality.ResultsOverall, 32 articles involving 55 197 women, met all inclusion criteria. Generally studies were well conducted and had a low risk of bias. The absolute risk of recurrent sPTB at <37 weeks' gestation was 30% (95% CI 27% to 34%). The risk of recurrence due to preterm premature rupture of membranes (PPROM) at <37 weeks gestation was 7% (95% CI 6% to 9%), while the risk of recurrence due to preterm labour (PTL) at <37 weeks gestation was 23% (95% CI 13% to 33%).ConclusionsThe risk of recurrent sPTB is high and is influenced by the underlying clinical pathway leading to the birth. This information is important for clinicians when discussing the recurrence risk of sPTB with their patients.
| S-EPMC5734267 | biostudies-literature